The objectives of the project are the creation of a reproducible aggregate brain culture system and its employment for the assessment of how metabolites related to mental retardation affect brain development and differentiation. Myelin synthesis and composition are being used as references of these events and because several inborn errors of metabolism are characterized as dysmyelination disorders. Variations in brain dissociation methods and culture media are being investigated to optimize cell survival and myelin synthesis. The aggregates are being chemically characterized to define their composition and to compare these features with the in vivo state. Cerebroside increase in aggregates during culture and S35 incorporation into sulfatide compared favorably with corresponding explant data.